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HISTORY
Germs, Dr. Billings, and the Theory of Focal Infection
Robert V. Gibbons
From the Department of Medicine, Madigan Army Medical Center,
Tacoma, Washington
Our understanding of infectious diseases continues to expand rapidly, and has led to the realization
that microorganisms are responsible for, or at least contribute to, numerous diseases that were never
before associated with infectious etiologies. However, a review of medical history reminds us that
this is not so novel an idea. Not long after the widespread acceptance of bacteriology and the germ
theory and with an increased awareness of public hygiene, there was a period during which it
seemed that nearly all diseases would prove to be the result of infections. One popular proposal
that championed such an idea was the theory of focal infection. This article reviews this theory by
considering the key concepts and developments that likely inspired it, and examines the work of
the theory’s most visible proponent, Dr. Frank Billings.
I have been made happy by discovering that I have only added to the observations of other physicians, in pointing
out a connection between the extraction of decayed and diseased teeth and the cure of general diseases.
— Benjamin Rush, 1809
The author of a recent perspective on infectious diseases
noted ‘‘a quieter revolution [that] has been taking place in
our understanding of human-microorganism interactions: the
discovery that transmissible agents are responsible for diseases
that were never suspected of being infectious in origin’’ [1].
Actually, this is not such a novel idea. During the early 1900s,
shortly after the widespread acceptance of the germ theory and
the principles of bacteriology, and with an increased awareness
of public hygiene, there was the expectation that most illness
would prove to be the result of infections. This idea crystallized
in the theory of focal infection. In brief, the theory proposed
that circumscribed foci of bacteria, localized to various parts
of the body, could result in a myriad of systemic diseases. Upon
review of this theory, the lesson for the modern practitioner is
clear: therapeutic interventions, even if based on current science, may not benefit patients.
As is true for theories today, the theory of focal infection
was a product of the intellectual environment of its time. The
theory was most dependent on the then recently developed
germ theory, but it was influenced as well by earlier ideas
associated with contagion and bacteriology. Another important
influence was probably that surgery was the primary therapy
The assertions contained herein are the opinions of the author and do not
reflect the official policy or position of the U.S. Department of the Army or
the U.S. Department of Defense.
Reprints or correspondence: Dr. Robert V. Gibbons, Department of Medicine, Madigan Army Medical Center, Tacoma, Washington 98499-5000.
Clinical Infectious Diseases 1998;27:627–33
This article is in the public domain.
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available during that era. Finally, its acceptance depended in
large measure on the proselytizing efforts of the theory’s most
visible proponent, Dr. Frank Billings. This article reviews the
theory of focal infection by considering the key concepts and
developments that served as its inspiration, and by examining
the life and work of Dr. Frank Billings.
Bacteriologic Influences
Frank Billings was born in 1854. In his home state of Wisconsin, he was employed as an elementary and high school
teacher, and he was destined to become a leader in medical
education. He entered the Chicago Medical College (now
Northwestern University Medical School) in 1878 and graduated in 1881 [2, 3]. At the time that Dr. Billings was completing
his medical studies, scientists were making enormous progress
in the field of bacteriology. Many had demonstrated the presence of bacteria in various disease states, observations that
led to the suspicion that bacteria were involved in pathologic
processes. The nature and extent of this involvement were the
source of heated debates among European academic circles. In
America, the germ theory continued to be largely ignored [4].
Robert Koch’s discovery of the etiology of tuberculosis was
seminal in convincing many of the causal role of bacteria in
disease and bringing recognition of the germ theory to America
[3]. This discovery occurred while Dr. Billings was completing
his internship at Cook County Hospital in Chicago and beginning his work as a demonstrator in anatomy at his alma mater
[2, 4]. In 1885, Dr. Billings, like many other American physicians before and after, sought to further his medical education
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at the great European universities. He moved to Vienna for a
year of clinical study and attended the lectures of influential
clinicians such as the venerated surgeon, Theodore Billroth.
Subsequently, he traveled to clinics in Paris and London and
met Louis Pasteur and Joseph Lister [4]. Given the recent
dramatic discoveries and the opportunity to learn from many
of the scientists who had made them, it is easy to imagine that
Dr. Billings’ ideas concerning health and disease would be
greatly influenced by the field of bacteriology as he embarked
on a career in academic medicine.
Dr. Billings manifested an appreciation for infectious diseases, from both a clinical and a public health perspective. In
two articles published in 1898, Dr. Billings seems to draw
parallels between sanitation for a city and hygiene for the body.
With respect to sanitation, he discussed the remarkable decline
in rates of cholera and other contagious diseases in Vienna
after the source of the water supply was changed from the
sewage-contaminated Danube River to pristine water from the
Alps. ‘‘Most of the infectious and contagious diseases may be
classified as preventable: most of them are filth diseases, and
they cannot exist in the presence of perfect cleanliness,’’ [5].
Concerning hygiene, he wrote ‘‘It is probably fair to state that
the great majority of diseases which we meet in our office
patients are caused by bad hygiene.’’ Unhygienic states, he
theorized, could lead to inflammation ‘‘of mucous membranes
or of the skin possibly, through the agency of bacteria, which
find a proper soil for development in or upon such weakened
tissues. When once under way, a resulting local process may
aggravate the complex whole and appear as a primary cause’’
[6]. He defined hygiene in a broad sense to include diet, air
quality, work habits, sleep patterns, social stressors, exercise,
shelter, and use of alcohol and tobacco.
In these articles, and in the subsequent development of the
theory of focal infection, Dr. Billings’ opinions reflect many
of the tenets of the hygienist Max von Pettenkofer, whose ideas
were well received in America [7]. Pettenkofer graduated with
a degree in medicine from the University of Munich in 1843,
and he began to conduct research in the field of medical chemistry at his alma mater in 1847. By the time he opened the first
Hygienic Institute in 1879, he had studied such diverse topics
as nutrition and metabolism; restoring aging paintings; copper
dental amalgam; the ventilation of houses; and the relation of
the atmosphere to clothing, habitations, and the soil. His work
with Munich’s water and sewer systems is credited for the
dramatic decrease in the city’s mortality rate associated with
typhoid fever between 1870 and 1898 [8].
Pettenkofer was extremely interested in the epidemiology of
intestinal diseases, particularly cholera. He believed that a germ,
which he termed X, must develop virulence in appropriate soil
(moist, porous soil with decaying organic matter was especially
effective) termed Y, before it became the toxic infectious substance termed Z. He also believed that individual susceptibility
or disposition to infection was an important factor in developing
an illness. Included among the important contributing factors
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Table 1. Focal infections leading to acute systemic disease noted
by Dr. Billings in 1912.
Focal site or type of
infection
Tonsil
Tonsil
Upper respiratory passage
Nasal mucosa
Diphtheria
Genitourinary tract
Tuberculosis
Systemic disease
Rheumatic joint infections
Endocarditis
Pneumonia
Epidemic meningitis
Nephritis
Gonorrheal arthritis
Disseminated (miliary) tuberculosis
suggested by Pettenkofer were advanced age, poverty, weakness,
bad air, unclean water, poor nutrition, improper clothing, physical
or mental strain, and excesses of all kinds [8].
Pettenkofer accepted the germ theory as it was being derived
by Koch and others but with some caveats. For example, he
accepted Koch’s comma bacillus as the germ (X) for cholera,
but believed that patient-to-patient transmission could not occur
until the bacillus became infectious (Z) by developing virulence
from the soil (Y). Pettenkofer believed so strongly in his ideas
that in 1892, at the age of 74, he drank one milliliter of fresh
culture derived from a patient who was dying of cholera. Subsequently, Pettenkofer developed only mild diarrhea and thus felt
further confirmation that the comma bacillus did not cause
cholera without first gaining virulence in the soil [8, 9].
It is of interest that Pettenkofer broached the idea of a cholera
carrier as early as 1869. He suggested that the germ could be
carried by a healthy person from a cholera region to an area
free of disease. There, an epidemic could ensue when the germ
became infectious after it was transmitted from that person to
the appropriate soil [8]. By the time Dr. Billings was writing
about focal infection, the concept of the ‘‘healthy’’ disease
carrier had been well established by investigators in Europe
and America [10].
Focal Infection
In an article published in 1906, Dr. Billings speculated that
some gastric and duodenal ulcers were caused by a bacterial
infection of the mucous membranes that rendered the cells
prone to digestion by the gastric juices [11]. A few years later,
he published a series of 12 cases of chronic endocarditis. He
noted that in four of these cases, tonsillitis or alveolar abscesses
occurred shortly before the onset of cardiac symptoms. Cultures
of blood from each patient had yielded streptococci, and Dr.
Billings postulated a relationship between the focal infections,
the positive blood cultures, and cardiac disease [12].
In 1912, in the introduction to the first article in which the
term focal infection was used in the title, Billings noted that
the principle that focal infection leads to acute systemic disease
was well established in medical science (table 1). However, he
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Theory of Focal Infection
was concerned that the concept of long-standing focal infection
leading to chronic systemic disease was not appreciated. He
wrote: ‘‘I think there can be no doubt that the insidious slow
degenerative processes which occur in many patients who arrive at the meridian of life are due to slow intoxications from
chronic focal infections variously located’’ [13]. He proposed
that ‘‘cardiovascular degeneration’’ was often caused by unappreciated chronic appendicitis. In this same paper he cited 16
cases of arthritis and nephritis among which foci of prolonged
infection were removed and clinical improvement followed
[13]. One year later, Billings published a general review of
arthritis deformans based on a study of 70 patients and opined
that this condition had an infectious etiology. In addition, he
indicated that improvement could be expected after removal
of the responsible focal infection [14]. To support his ideas,
Dr. Billings pointed to the work of Dr. Edward C. Rosenow,
a colleague with whom he collaborated extensively.
Rosenow, who was born in Wisconsin 21 years after Billings,
graduated from Rush Medical College in 1902 (where Dr. Billings was Dean) and served his internship at Presbyterian Hospital (where Dr. Billings was an attending physician). From 1904
to 1915, Rosenow was a member of the staff of the McCormick
Memorial Institute for Infectious Diseases (where Dr. Billings
served as the president of the board) [4, 15]. In Dr. Billings’
words:
In acute rheumatism the bacteria obtained from joint exudate
and from rheumatic nodes have been studied by Dr. Edward C.
Rosenow. . . . He has found that organisms from rheumatism
appear to occupy a position between S. viridans and S. hemolyticus. They are more virulent than the former and less virulent
than the latter. Three types of organisms have been isolated from
rheumatism. . . . By varying the condition of growth, these
types may be changed quite readily, one into the other. [14]
In animal studies, Dr. Rosenow sought to fulfill Koch’s postulates. First, he cultured an organism from the implicated site
of focal infection (e.g., teeth or tonsils) or distant systemic
lesions (e.g., joints) of patients. Next he injected animals intravenously with the bacteria cultured from the human lesions
and found that the bacterial strains produced lesions in the
organs of animals that corresponded to those organs of patients
from whom the bacteria were isolated. On the basis of these
observations he set forth the theory that specific bacteria had
a pathogenic affinity for certain tissues, a characteristic he
termed elective localization [16]. Dr. Rosenow also coined the
term bacterial transmutation to explain the observation that
streptococci and pneumococci appeared to change from one to
the other. He found this to be especially common on serial
passages of the bacteria through animals or with variations in
oxygen tension or temperature. For Dr. Billings and Dr. Rosenow, bacterial transmutation explained the discordant results
among the studies by many investigators who had described a
variety of streptococcal organisms isolated from arthritic patients [14].
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While searching for the etiology of polio, Rosenow found a
pleomorphic coccus isolated from the adenoids and tonsils that
formed all gradations between a large coccus or diplococcus on
aerobic culture to exceedingly small, almost ultramicroscopic,
‘‘globoid’’ forms, on anaerobic culture [17]. Contributing to
the clinical importance of transmutation was the fact that this
transformation could apparently occur in a primary focus of
infection such as a tonsil. Thus, theoretically, a nonvirulent
bacteria could become virulent and cause systemic disease, or
a germ could mutate, thereby changing its elective localization
and cause disease in a different target organ. Clinical application of this concept of transmutation provided the impetus to
remove all focal infections, even those that occurred without
current systemic illnesses [18].
The ideas of Billings and Rosenow were consonant with the
concept of a disease-carrier state. In their scenario, however,
the carrier does not transmit the germ to another, but rather
harbors an organism that has the potential to cause disease
within the carrier at any time. Their scenario also echoes Pettenkofer’s idea that to become infectious germs require some other
factor from the soil. In this case the ‘‘soil’’ would be the
inflamed and weakened tissues of the body. Like Pettenkofer,
Billings and Rosenow believed that individual susceptibility to
infection occurred on the basis of a variety of hygienic factors,
and that bacterial virulence could change given the right conditions.
Pleomorphic Bacteria
The notion that bacteria were pleomorphic was not new. In
the mid-1800s it had been observed that the same fungus appeared in several different forms. Furthermore, early culture
methods could not produce pure cultures. Hence, initially one
organism might become apparent, but soon the culture would
yield a variety of organisms. Because these additional organisms were not recognized as contaminants, the concept emerged
that fungi and bacteria could readily change their morphology
and transform from one into another [19, 20].
During the mid-1800s, Ernst Hallier, a botanist and prolific
writer in Germany, believed that microscopic organisms were
stages in the development of more complex fungi, and that
transformations were brought about by changes in medium,
moisture, and temperature [19]. Billroth, whose lectures Billings had attended in Vienna, was a strong proponent of the
position that all round and rod-shaped bacteria were stages of
the same organism, which he called Coccobacteria septica,
because of the occurrence of the organism in putrid fluids and
septic wounds. In addition, he believed that changes in the
organisms occurred according to different environmental conditions. Edwin Klebs, a professor of pathological anatomy at
Rush Medical College from 1896 to 1900 (likely to have known
Billings), was a supporter of Billroth’s idea [19]. Despite the
opposition of some (e.g., Koch and Ferdinand Cohn) the concept of pleomorphic bacteria was widely held in America in
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Table 2. Diseases resulting from focal infections according to Dr.
Billings in 1914 and 1915 and later by others.
Additions as of
1915
In 1914
Arthritis
Myositis
Acute rheumatism
Nephritis
Visceral degeneration
Septicemia
Gastric and duodenal ulcers
Cholecystitis
Myocarditis
Endocarditis
Thyroiditis and goiter
Pancreatitis
Chorea
Appendicitis
Erythema nodosum
Herpes zoster
Spinal myelitis
Osteomyelitis
Iridocyclitis
Suggested by others
Psychoses
Phobias
Melancholia
Insomnia
Arrhythmias
Hypertension
Cardiac insufficiency
Angina
Paresthesias
Hodgkin’s disease
Polio
the late 1800s [7, 20]. Undoubtedly, the work of its supporters
lent credence to Rosenow’s and Billings’ concept of pleomorphism.
The Theory of Focal Infection
In a 1914 article that was read before the American Medical
Association (AMA) Section on Practice of Medicine and published as a lead article in the association’s journal, Dr. Billings
expanded the theory of focal infection to include many more
diseases (table 2) [21]. In an accompanying article, Dr. Rosenow detailed complicated culture methods that yielded positive results from cultures of blood and tissue for a variety of
diseases, whereas those cultures performed in the usual fashion
remained sterile [22].
In 1915, at the Lane Lectures in San Francisco, Dr. Billings
provided perhaps the most complete description of the theory
of focal infection. He defined a focus of infection as a circumscribed area of tissue containing pathogenic organisms that
could occur anywhere in the body, but usually occurred in the
head because the mouth and airways were frequently exposed
to infectious agents. Teeth, especially those subjected to excessive dental work, and tonsils were particularly vulnerable. Alveolar abscesses were important given that they were often not
noticed by patients. The lungs, the genitourinary tract (especially the prostate and seminal vesicles), and the gastrointestinal tract (e.g., the appendix or gallbladder) were other common
sites of occult infection. Secondary foci in lymph nodes adjacent to the primary focus could also occur. Systemic disease
occurred when bacteria from these focal infections were disseminated to distant organs, either hematogenously or via the
lymph [23].
For example, Dr. Billings believed that acute appendicitis
was a hematogenous infection of the appendix from a distant
focus such as the teeth or tonsils. Subsequent chemotaxis and
leukocyte invasion led to the obstruction, which in turn resulted
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in the increased growth of saprophytic anaerobes and the clinical scenario of fulminant appendicitis. The appendix could also
be a primary focus of infection and was frequently implicated
as a potential cause of cardiovascular degeneration. In peptic
ulcer disease, bacteria from distant sites localized in the stomach and caused small microhemorrhages, and ulcerative
changes occurred on the basic of the presence of bacteria and
the action of gastric juices on the damaged mucosa. Similarly,
chronic arthritis was caused by a hematogenous spread of bacteria to the joints. Once present, the bacteria caused small
hemorrhages and a consequent decrease in oxygen and nutrients
in the tissues. This environment was favorable for further bacterial growth and promoted retrograde metabolism, which turned
soft tissues into bone [23].
The nature of the discussions that followed the presentations
of these articles concerning focal infection implied that the
theory might explain any poorly understood disease. Indeed,
the theory of focal infection was considered by many physicians as an explanation for psychosis/mental illness [24], phobias, melancholia, insomnia [25], arrhythmias, angina, cardiac
insufficiency [25, 26], paresthesias [26], high blood pressure
[27], anemia [28], Hodgkin’s disease [29, 30], and polio [17].
Repeated, thorough physical examinations were recommended
to search for a focus of infection in any patient with a puzzling
systemic disease. The roentgen ray; ear, nose, and throat specialists; fluoroscopic bismuth tests; and bacterial cultures were
suggested as promising methods to find these elusive foci [31].
Dr. Rosenow recounted his search for a focus of infection in
one patient this way:
. . . the patient had gone through the search for foci of infection;
his tonsils had been removed, the teeth examined, and a thorough
physical examination made. The patient had had repeated attacks
of rheumatism which continued for years, and usually occurred
in the fall. He came to me in the midst of one of these attacks
and on examination I was unable to find any focus of infection
that would account for the trouble. This particular attack followed
some intestinal disturbance. On three occasions I was able to
isolate from the intestinal tract a streptococcus which when injected into animals produced rheumatism. This attack cleared up
and I immunized the patient for a long time with the vaccine
prepared from the streptococcus from his stool in the hope that
some unknown focus in the intestinal tract might clear up.
This patient went south, and while in the South he had some
trouble with his teeth. He saw a dentist . . . and he found an
abscessed tooth and pockets of pyorrhea. When he came back I
examined the mouth carefully and found no evidence of infection
until along the surface of the gums I raised the tissues and found
pus pockets. There was not even inflammation on the surfaces,
but with a probe I obtained pus from the pockets around the
teeth from which I made a culture and produced rheumatism in
an animal. The pyorrhea probably existed for years. This illustrates how difficult it is to locate the focus. [32]
The recommended management of focal infections included
both methods of prevention and eradication. Prophylactic measures focused on both individual hygiene and environmental
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Theory of Focal Infection
considerations. According to Dr. Billings, ‘‘carious teeth are
an inexcusable evidence of faulty personal cleanliness in those
otherwise healthy’’ [31]. The use of crowns and other dental
measures, which would likely harbor infectious foci, were to
be abandoned [31]. Enlarged or infected tonsils and adenoid
overgrowth were considered a menace to health. In fact, the
abundance of lymphoid tissue in children was believed to explain the frequency of rheumatic fever, diphtheria, and tonsillitis at that time of life [13]. Environmental factors were also
considered important in the prevention of infection. Pure air
and wholesome foods were recommended to replace the protein
of wasted tissues and to boost the immune system. Overfatigue
and exposure to extreme temperatures, especially prolonged
exposure to cold temperatures, were believed to lower host
resistance and increase bacterial virulence and should thus be
avoided [14, 16, 23].
If a focal infection was found, the therapy was surgical
removal. Although autogenous vaccines and polyvalent streptococcal horse serum had been used therapeutically, the value of
these were limited by side effects (including anaphylaxis), and
neither seemed effective without removal of the infection focus
[31]. More than a decade earlier, Billings had lamented that
therapeutic medicine was rarely able to intercede in infectious
disease. Thus, he became an unabashed champion of surgery:
‘‘bacteriology has made possible a knowledge of true cleanliness which has enabled the surgeon to invade with impunity
every part of the human body. Hence, the horizon of surgery
is wide and its limitations now are few’’ [5]. Dr. Billings
described some of the measures used to remove focal infections:
Tonsillectomy: oral surgery for alveolar abscesses (roentgenography will show jaw disease); drainage or other measures to
cure sinusitis; vasectomy to drain and to use the vas deferens to
wash out infected seminal vesicles and to drain the prostate gland;
and any other measures necessary to surely remove all possible
streptococcus foci of infection have been made use of. [14]
The net result of the influence of the focal infection theory
was a boom in tonsillectomies, tooth extractions, and sinus
procedures. So widespread was this practice that one contemporary is quoted as saying, ‘‘If the craze for violent removal goes
on, it will come to pass that we will have a gutless, glandless,
toothless, and I am not sure that we may not have, thanks to
false psychology and surgery, a witless race’’ [33].
The Theory of Focal Infection in Perspective
By the early 1900s the field of bacteriology had provided
etiologies for many diseases not previously understood. In
addition to tuberculosis and cholera, other diseases discovered in the early years of clinical bacteriology were diphtheria, tetanus, plague, dysentery, syphilis, and whooping cough.
An increased understanding and practice of public hygiene
resulted in decreased rates of disease. With such an auspi-
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cious start, the germ theory may have been seen as the key
to deciphering most, if not all, diseases. The theory of focal
infection was an extension of the germ theory that offered
physicians potential explanations for poorly understood illnesses. Indeed, the theory has proven to be valid in some
instances (e.g., streptococcal pharyngitis and acute rheumatic
fever). More recently recognized examples include GuillainBarré syndrome after infection due to Campylobacter jejuni
[34], hemolytic-uremic syndrome after infection due to Escherichia coli O157:H7 [35], and cryoglobulinemia associated
with hepatitis C infection [36].
As it turned out, the germ theory was not the key to every
disease. Dr. Rosenow’s work, viewed from the perspective of
modern bacteriology, was obviously flawed; it was fraught with
contamination, which affected the isolation and identification
of organisms. However, in that era, his efforts appeared to
represent significant advances in a new technology with great
potential. Frequently, the theory of focal infection was presented in lead articles in the Journal of the American Medical
Association, and the theory was accepted by other prominent
physicians of the period such as Charles Mayo and Russell
Cecil, thereby further enhancing its credibility [24, 37].
Logically, our concept of disease dictates our response to
disease. It may also be true that the ways in which we are able
to respond to disease at least in some measure shape our concepts of disease. The theory of focal infection not only explained puzzling disease, but also advocated treatment that was
available to patients at that time, namely, surgery and attention
to individual hygiene. A contemporary pathologist described a
focus of infection as ‘‘anything that is readily accessible for
surgery’’ [38]. It could also be argued that economics may have
contributed to the acceptance of this theory. One bacteriologist
stated that ‘‘The age of specialization stimulates surgery. Operations carry the best fees with them, and without intimating
that economics play a role in the specialist’s decision, nevertheless it is only reasonable to regard him as human — if he is the
proud possessor of surgical skill, he is more prone to use it’’
[33].
In addition, when considering the popularity of the theory,
it should be noted that Dr. Billings was a prolific and wellrespected contributor to academic and organized medicine, both
locally and on a national level. Early in his career he was
professor of physical diagnosis and medicine at Northwestern
University Medical School. Later he was professor of medicine
and dean of the faculty at Rush Medical College, and he was
an attending physician at Cook County Hospital, St. Luke’s
Hospital, and Presbyterian Hospital. He served as both president of the Chicago Medical Society and as president and
treasurer of the AMA during a time of rapid membership
growth. In 1900 there were 8,000 members of the AMA; by
1910 there were 70,000 members, as many as 50% of American
physicians [39]. Billings was accorded the distinct honor of
receiving an invitation to deliver the Shattuk Lecture in Boston
during his tenure as AMA President. He spoke about medical
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education, a result of his involvement in creating the Council
on Medical Education and Hospitals, which eventually led to
the famous Flexner Report [2, 3].
The Decline and Epilogue
Eventually the support for the theory of focal infection declined. Even at the zenith of the theory’s popularity, some
expressed concern: ‘‘Since the discovery of a positive relationship between tonsil infections and secondary manifestation in
other organs and parts, tonsils have been removed wholesale,
in some instances on slight provocation. Their removal has,
we fear, become almost a fad’’ [40]. By the mid-1920s more
were beginning to believe that the theory was being carried
too far [41]. With further progress in the field of bacteriology,
the research that supposedly supported the theory was increasingly discounted. The studies were not reproducible and questions arose concerning mixed cultures in Dr. Rosenow’s work.
In 1928, W. L. Holman effectively discredited the concept of
elective localization. He pointed out inconsistencies among the
data of studies supporting the theory, including incongruities
in tables that reported results. In addition, he noted the difficulties in applying results of animal studies to human disease,
and questioned the variability in bacterial doses used in the
studies and the timing of animal sacrifice [42].
During the 1930s the perspective of focal infection changed
in relation to arthritis. In a review of chronic arthritis in 1935,
Chester Keefer indicated that he doubted that focal infection
was related to arthritis [43]. Others who reviewed the data
found them controversial but favored a more conservative therapeutic approach than advocated earlier [44]. Russell Cecil
reversed his view on focal infection. In 1938, in a study of
200 cases of rheumatoid arthritis Cecil and D. Murray Angevine found that for 70% of cases there was absolutely no evidence of focal infections. Retrospectively, they found that 46%
of the patients had had their tonsils removed (although only
15% provided any history of tonsillitis or complained of sore
throats), and 26% had had teeth removed because of arthritis.
Prospectively, among those patients with focal infections treatment of such did not provide any benefit for the arthritis. In
addition, when attempting to duplicate Rosenow’s studies,
these investigators were unable to induce significant arthritis
in animals with use of bacteria obtained from patients with
rheumatoid arthritis. They concluded that chronic focal infection was relatively unimportant in rheumatoid arthritis and that
complete reevaluation of the focal infection theory was indicated: ‘‘Many of us who originally accepted the theory of focal
infection with enthusiasm have watched with interest and some
trepidation its rapid development in the various fields of medicine but are now wondering if the time has not arrived for a
revaluation of the whole theory’’ [38].
In 1940, Hobart A. Reimann and W. Paul Havens systematically reviewed the literature and made a case against indiscriminate removal of teeth and tonsils. They documented other stud-
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ies that supported Holman’s discrediting of elective localization
and detailed the difficulties in assessing bacteriologic and radiological criteria for infected teeth and tonsils. They cited
multiple observational and controlled studies that demonstrated
a lack of benefit with removal of teeth and tonsils, and the
potential harm associated with such procedures [41].
A review of two texts of the period illustrates the rise and
fall of this theory. In the 1915 edition of Osler’s The Principles
and Practices of Medicine, there is no specific reference to
focal infection. The only local infections referred to are tetanus,
diphtheria, erysipelas, and pneumonia [45]. The 1920 edition
contains a discussion of focal infection that is consistent with
Dr. Billings’ concepts [46]. However, in the 1940 edition, the
discussion is preceded by a comment that focal infections as
an explanation for many subacute and chronic diseases is on
the wane and many are skeptical of such a relationship [47].
Similarly, in 1934, the Merck Manual discusses focal infection
and mentions 35 conditions that may result [48]. In the 1940
edition, focal infection is included only as a subset of septicemia, and there is no mention of the role of focal infection in
chronic disease [49]. The 1950 edition makes no mention of
focal infection [50].
At the turn of the century, during the dawn of bacteriology,
it appeared that most if not all diseases might be infectious in
origin. In time it became clear that the theory of focal infection
carried this concept to an extreme. Ultimately, it was demonstrated that the science on which the theory was based was
flawed. Indeed, infections could not explain all diseases. However, the last chapter in this interesting story may not yet be
written. Current technology has demonstrated an association
of specific infectious agents to many diseases not recently considered infectious. There is a reconsideration of the association
of infectious agents in ulcer disease, neurologic illnesses, some
types of arthritis, malignancies, vascular disorders, and even
coronary artery disease [1]. History reminds us to consider
whether these apparent associations might be merely the result
of our lack of experience with new technologies. History also
demonstrates that therapeutic interventions, even if based on
the most current scientific understanding of etiology and pathology, may not result in improved health of patients. Prospective studies still need to be undertaken. Nevertheless, the words
of Dr. Billings from 1915 sound almost prophetic: ‘‘Modern
bacteriology and clinical research are adding day by day incontestable proof that bacterial invasion and infection of tissue is
the fundamental cause of many of the systemic diseases, which
have been classed as toxic, metabolic or nutritional’’ [23].
Acknowledgments
The author would like to thank Dr. Ron Cooper for his thoughtful review of this manuscript, Dr. Robert Joy and Dr. Dale Smith
for encouraging the study of the history of medicine, and Lisa
Oberg and Colleen Weum for assistance with reference materials.
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CID 1998;27 (September)
Theory of Focal Infection
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